Trial record 1 of 10 for:    "Angelman syndrome"
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A Trial of Levodopa in Angelman Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Rady Children's Hospital, San Diego
University of California, San Francisco
Baylor College of Medicine
Vanderbilt University
Greenwood Genetic Center
Children's Hospital Medical Center, Cincinnati
Angelman Syndrome Foundation, Inc.
Information provided by (Responsible Party):
Wen-Hann Tan, Children's Hospital, Boston
ClinicalTrials.gov Identifier:
NCT01281475
First received: January 20, 2011
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

This study is designed to determine whether levodopa will lead to an improvement in the development and tremor in children with Angelman syndrome (AS).

It has been suggested that levodopa, a medication that is usually used to treat Parkinson disease in adults, may help children with AS in their overall development and reduce the tremor that some of them have.

If levodopa is found to be beneficial for children with AS, this could lead to a new treatment for AS.

Funding Source - FDA-OOPD


Condition Intervention Phase
Angelman Syndrome
Drug: Levodopa/carbidopa
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • Developmental Outcome Measures [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Changes in raw or standard scores between baseline and after 12 months of treatment with either placebo or LD/CD of:

    I. Bayley Scales of Infant and Toddler Development, 3rd edition (or the Mullen Scales of Early Learning in the more developmentally advanced subjects) II. Vineland Adaptive Behavior Scales, 2nd edition (standard scores only) III. Preschool Language Scale, 4th edition IV. Aberrant Behavior Checklist - Community version


  • Tremor and Movement Disorder [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Changes in raw score of a modified Unified Parkinson's Disease Rating Scale (mUPDRS), a measure of tremor and movement disorder, from baseline after 12 months in the placebo or the LD/CD group.


Secondary Outcome Measures:
  • EEG [ Time Frame: 12 months, 24 months ] [ Designated as safety issue: No ]
    Changes in electroencephalogram (EEG) scores at 12 months and 24 months.


Estimated Enrollment: 100
Study Start Date: January 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Levodopa
Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa.
Drug: Levodopa/carbidopa

Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

Other Names:
  • Sinemet
  • L-dopa
Placebo Comparator: Placebo
The placebo (in this study, microcellulose) is not expected to have any effect.
Drug: Levodopa/carbidopa

Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

Other Names:
  • Sinemet
  • L-dopa

Detailed Description:

Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Animal studies have suggested that levodopa can reverse the excess phosphorylation of some enzymes involved in synaptic and neuronal function, including calcium/calmodulin-dependent kinase type 2 (CaMKII).

Recently, it was shown that excess phosphorylation of CaMKII may be responsible for some of the neurological deficits seen in Angelman syndrome. Therefore, it is hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.

Although many children have used levodopa for a variety of medical conditions over the last 30 years, it has not been approved by the Food and Drug Administration (FDA) for use in children, and it has not been formally studied in children with Angelman syndrome.

Therefore, the purpose of this study is to find out whether levodopa will lead to an improvement in the development and in the tremor in children with AS.

  Eligibility

Ages Eligible for Study:   4 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 4 years and 12 years (i.e., before the 13th birthday)
  2. Molecular confirmation of the diagnosis of AS, which may include abnormal methylation studies or UBE3A mutation analyses - only subjects with a molecular diagnosis will be allowed to enroll
  3. Not on LD, CD, or any dopamine agonists in the 2 weeks prior to participation

Exclusion Criteria:

  1. Co-morbid disorders that may be associated with developmental or cognitive delays
  2. Poorly controlled seizures - An average of more than 2 clinical seizures per month in the 12 months prior to enrollment.
  3. Use of medications that may interact with LD/CD including atypical antipsychotics (aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, risperidone, ziprasidone), monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine), or phenytoin within the last 14 days, or other investigational interventions within the past 3 months
  4. Presence of cardiovascular disease or instability, respiratory disease, liver disease, peptic ulcer disease, renal impairment, or hematological disorders
  5. Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281475

Locations
United States, California
Rady Children's Hospital, San Diego
San Diego, California, United States, 92123
University of California, San Francisco
San Francisco, California, United States, 94121
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, South Carolina
Greenwood Genetic Center
Greenwood, South Carolina, United States, 29646
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Wen-Hann Tan
Rady Children's Hospital, San Diego
University of California, San Francisco
Baylor College of Medicine
Vanderbilt University
Greenwood Genetic Center
Children's Hospital Medical Center, Cincinnati
Angelman Syndrome Foundation, Inc.
Investigators
Principal Investigator: Wen-Hann Tan, BMBS Children's Hospital Boston
Principal Investigator: Lynne M. Bird, MD Rady Children's Hospital, San Diego
Principal Investigator: Steven A. Skinner, MD Greenwood Genetic Center
Principal Investigator: Carlos A. Bacino, MD Baylor College of Medicine
Principal Investigator: Anne Slavotinek, MD University of California, San Francisco
Principal Investigator: Gregory Barnes, MD Vanderbilt University
Principal Investigator: Logan Wink, M.D Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Wen-Hann Tan, Attending Physician in Genetics, Children's Hospital, Boston
ClinicalTrials.gov Identifier: NCT01281475     History of Changes
Other Study ID Numbers: 09-12-0610, 3523
Study First Received: January 20, 2011
Last Updated: November 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:
Angelman syndrome
Levodopa
Carbidopa
L-dopa

Additional relevant MeSH terms:
Angelman Syndrome
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Carbidopa
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 31, 2014